Endogenous peptide: Met-enkephalin-Arg-Phe, differently regulate expression of opioid receptors on chronic treatment

Vats, Ishwar Dutt; Chaudhary, Snehlata; Karar, Jayashree; Nath, Mahendra; Pasha, Qadar; Pasha, Santosh

doi:10.1016/j.npep.2009.07.003

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Volume 43, Issue 5 , Pages 355-362, October 2009

Endogenous peptide: Met-enkephalin-Arg-Phe, differently regulate expression of opioid receptors on chronic treatment

Ishwar Dutt Vats
- Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Delhi, India
- Department of Chemistry, University of Delhi, Delhi, India
Snehlata Chaudhary
- Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Delhi, India
Jayashree Karar
- Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India
Mahendra Nath
- Department of Chemistry, University of Delhi, Delhi, India
Qadar Pasha
- Functional Genomics Unit, Institute of Genomics and Integrative Biology, Delhi, India
Santosh Pasha
- Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Delhi, India
- Corresponding author. Address: Peptide Synthesis Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India. Tel.: +91 011 27666156; fax: +91 011 27667471.

Received 13 March 2009; accepted 26 July 2009. published online 28 August 2009.

Abstract

Endogenous peptide, Met-enkephalin-Arg-Phe (Tyr-Gly-Gly-Phe-Met-Arg-Phe; MERF) induces effects like antinociception, inhibit contraction of guinea pig ileum, mouse vas deferens and anti-tussive action. However, results regarding its functional efficiency and selectivity are controversial. Therefore, present study was undertaken to investigate whether MERF on systemic (intra-peritoneal, i.p.) route of administration induce any antinociception or not; to scrutinize the effect of 6days chronic i.p. treatment of MERF on expression of μ (MOR1), δ (DOR1) and κ (KOR1) opioid receptors; and finally, the antinociceptive effect of two synthetic peptides, MERFamide and (D-Ala²)-MERFamide was compared with MERF on intracerebroventricular administration in order to understand the role of FMRF moiety in analgesic effect of MERF.

Pharmacological results revealed that only 68.4 and 91.2μmol/kg dose induce significant antinociception among various doses. Further, on 6days chronic treatment, MERF induced significant antinociception in comparison to saline. Differential expression of MOR1 and KOR1 showed continuous up-regulation throughout the treatment whereas DOR1 showed down-regulation in initial 3days followed by subsequently up-regulation during the latter observable period. Moreover, variation in opioid receptors expression had not affected the MERF antinociception.

In conclusion, present study discursively demonstrates that MERF during chronic treatment interacts with all three opioid receptors (μ, δ and κ) in rats and differently regulates their expression. Further, the interaction was such that the induction was mainly observed at molecular/expression level and not at pharmacological level to affect antinociception.

Keywords: Met-enkephalin, MERF, Opioid receptor regulation, Antinociception